What Is Preclinical Research?

Before a new medicine is given to people, there is a stage of research that happens largely outside the clinic. This is known as preclinical research.

It is the point where researchers start asking some fairly important questions: How does a potential treatment behave in a biological system? Does it produce the effect researchers are looking for? What happens to it once it enters the body? And, perhaps most importantly, are there signs that it could cause harm?

Preclinical research does not prove that a treatment will work in humans. It is not a smaller version of a clinical trial. Instead, it builds the evidence needed to decide whether moving into human studies is scientifically and ethically justified. The FDA describes preclinical research as laboratory and animal testing used to answer basic questions about safety before clinical research begins.

What happens during preclinical research?

There is no single experiment that makes up preclinical research. It is usually a collection of studies, with each one looking at a different part of the picture.

Some work takes place in vitro, meaning outside a living organism. Researchers might study cells, tissues or other biological systems to see how a compound interacts with them. Researchers can use these experiments to investigate a proposed mechanism of action, identify biological responses, and determine which questions require further exploration.

Other studies are in vivo, where the compound is investigated in a living organism. Animal studies can provide information that cannot always be obtained from cells alone, particularly when researchers need to understand how different parts of the body respond together.

Modern non-clinical research can also involve approaches such as organoids, 3D tissue models, ex vivo systems and computational or in silico methods. The EMA encourages the use of appropriate alternatives to animal studies where they can provide meaningful information, while recognising that animal models may still have a role where they are scientifically justified.

So, despite the phrase “preclinical research” sometimes being used as though it means animal testing alone, the reality is broader.

What are researchers trying to find out?

Safety is a major part of the work, but it is not the only consideration.

Researchers may investigate pharmacology, looking at what the compound does in the body and whether it produces the biological response expected from its proposed mechanism. They can also examine pharmacokinetics — in simple terms, what the body does to the compound.

That can include absorption, distribution, metabolism and excretion. Researchers may want to know how quickly a substance enters the bloodstream, where it goes, how it is broken down and how it eventually leaves the body.

Toxicology is another key area. Studies may look for potentially harmful effects, including whether toxicity appears at particular doses or after repeated exposure. Depending on the medicine and its development stage, additional investigations can include genotoxicity, effects on particular organs, local tolerance and other specialised safety assessments. The EMA’s non-clinical guidance covers areas including pharmacology, pharmacokinetics, toxicology and safety pharmacology.

The aim is not simply to produce a long list of test results. Researchers need to understand what those results mean in the context of a potential first-in-human study.

Why are animal studies used?

Animal research has a specific role in some areas of preclinical development because a living organism can reveal effects that cannot be captured fully in isolated cells.

For example, a compound might appear promising in a cell-based experiment but behave differently once it is absorbed, metabolised or distributed throughout a whole body. Animal studies can help researchers investigate these wider effects.

That does not mean an animal result automatically predicts what will happen in humans. Species can differ considerably in physiology, metabolism and response to a particular compound. Choosing an appropriate model is therefore an important scientific decision.

Regulatory guidance also places emphasis on using animals responsibly. The principles of the 3Rs — replacement, reduction and refinement — are relevant to non-clinical research. Where suitable alternatives exist, researchers should consider them; where animals are necessary, studies should be designed carefully to obtain useful information while avoiding unnecessary use.

The FDA notes that, in drug development, animal testing may involve more than one species because a medicine can affect different species in different ways. Such studies can provide information on pharmacology, toxicity, metabolism and excretion.

Preclinical research is not the same as clinical evidence.

This distinction matters.

A treatment can produce an interesting result in cells or animals without producing the same result in humans. Biological systems are complicated, and translating findings from a laboratory model to people is not straightforward.

For that reason, phrases such as “shown to work in preclinical studies” need to be read carefully. They describe evidence from a particular research setting, not established clinical effectiveness.

Preclinical findings can support the decision to begin human research, but clinical trials are where the treatment is actually investigated in people. The FDA describes the purpose of preclinical work as developing enough information to support a decision about whether it is reasonably safe to proceed to initial human studies.

The EMA similarly focuses on managing uncertainty and potential risks before an investigational medicine is first administered to humans.

When does preclinical research end?

There is not always a neat dividing line.

As a potential medicine progresses through development, researchers build an increasingly detailed package of non-clinical evidence. The exact studies required can depend on the type of product, its intended use, how it is administered and the stage of development.

For conventional medicines, international guidance such as ICH M3(R2) sets out recommendations for non-clinical safety studies used to support human clinical trials and later marketing authorisation.

The results are then considered alongside other information before a clinical trial can begin. This can include manufacturing information, the proposed clinical protocol and details about how the investigational product will be administered and monitored.

In other words, preclinical research is not simply a box that researchers tick before starting a clinical trial. It is part of an ongoing evidence-building process.

Why does preclinical research matter?

Preclinical research serves a crucial purpose: it addresses a challenging question before individuals are exposed to a new treatment: what do we know, and what do we still not know?

It can identify promising biological effects. It can reveal toxicity that might otherwise go unnoticed. It can help researchers understand dosing, metabolism and potential risks. Just as importantly, it can show when an idea needs more investigation rather than being taken straight into human testing.

But its limitations are just as important as its potential.

A positive laboratory or animal study is an encouraging research finding, not proof of a treatment’s effectiveness in people. Likewise, a negative result may raise questions about a particular compound, model or mechanism without necessarily answering every question about the underlying science.

That is why preclinical evidence is best viewed as one stage in a much larger research journey — valuable for reducing uncertainty, but not a substitute for evidence from well-designed clinical studies.